To summarize, the current study demonstrates that BRCA1 positively regulates FOXO3 expression through inhibiting the activity of ESH2 in breast cancer, whereas depletion or mutation of BRCA1 would lead to restoration of the ability of EZH2 to recruit DNMT1/3a/3b methyltransferases and H3K27me3 histone marks, to mediate methylation and silencing of the FOXO3 gene. This evidence concerns the gene BRCA1 and breast cancer.